Release of such cytokines as tumor necrosis factor a (TNF-.alpha.) and transforming growth factor .alpha. (TGF-.alpha.) can cause adverse reactions ranging from psoriasis to sepsis. Many of these reactions are related to inflammation or autoimmune conditions, such as psoriasis and arthritis.
Hydroxamic acid derivatives are known to have some inhibitory effect against certain cytokines, however they also inhibit matrix metalloproteinase enzymes (MPPs) such as collagenases, stromolysins, and gelatinases, leading to undesirable side effects. Thus it is desirable to find compounds capable of inhibiting TNF-.alpha. and TGF-.alpha. which do not have these side effects. In contrast to structurally related hydroxamic acid derivatives, the hydrazine derivatives provided by the present invention show only weak inhibitory activity against the matrix metalloproteinase (MMP) family of enzymes, such as collagenases, stromelysins and gelatinases.